1. Field of the Invention
The present invention relates to an agent for protecting cartilage, i.e., a chondroprotective agent, more particularly, a chondroprotective agent containing a carboxylic acid compound of the general formula (I) as mentioned below or a cis- or trans-isomer thereof, or a pharmaceutically acceptable salt or ester thereof.
2. Description of the Related Art
There are various types of arthropathy, for example, rheumatoid arthritis, rheumatic fever, and osteoarthritis. Many people particularly suffer from rhematoid arthritis and osteoarthritis. These diseases have been studied as the major types of arthropathy. There are congenital and secondary osteoarthritis, and further primary osteoarthritis caused by degeneration of the articular cartilage along with aging. Patients suffering from primary osteoarthritis have recently been increasing along with the increase in the population of the aged.
Although there are considerable differences of the causes and conditions between rheumatoid arthritis and osteoarthritis, the articular function becomes eventually obstructed by the destruction of the cartilage in both of rheumatoid arthritis and osteoarthritis.
The first choice of medicines for the treatment of rheumatic diseases such as rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, and osteoarthritis are analgesic and anti-inflammatory agents, for example, aspirin or indometacin. Further, gold compounds such as Shiosol, immunomodulators, steroids, or D-penicillamine are used as medicines for the treatment of rheumatoid arthritis.
The above conventional analgesic and anti-inflammatory agents, however, were not effective against the destruction of the articular cartilage, and in fact, sometimes exhibited adverse effects in experiments using chondrocytes. Further, no inhibitory effect on the destruction of articular cartilage was observed in the above medicines for the treatment of rheumatoid arthritis.
It is known that caffeic, ferulic, isoferulic, or 3-ethoxy-4-hydroxycinnamic acid may be used in the following pharmaceutical applications: Caffeic and ferulic acids exhibit an antiviral activity [Japanese Unexamined Patent Publication (Kokai) No. 4-234319]. Caffeic acid may be used as a calcium antagonist [Japanese Unexamined Patent Publication (Kokai) No. 4-243822], an anti-allergenic agent [Japanese Unexamined Patent Publication (Kokai) No. 59-155314], and the like. Caffeic acid and methyl caffeate can be used for the treatment of autoimmune disorders (WO91/17749). Further, ferulic and isoferulic acids may be used as an antitumor agent for preventing drug resistance in immunochemotherapy [Japanese Unexamined Patent Publication (Kokai) No. 56-115716]. Further, ferulic acid may be used as a composition for mitigating hyperlipemia and platelet aggregation (U.S. Pat. No. 4,842,859). Further, ferulic acid and esters thereof exhibit an anti-inflammatory action (A. S. Chawla et al., Indian J. Exp. Biol., Vol. 25, No. 3, pp. 187 to 189, 1987). 3-Ethoxy-4-hydroxycinnamic acid may be used as an ultraviolet absorbent for cosmetics [Japanese Unexamined Patent Publication (Kokai) No. 64-13018].
The above carboxylic acids, the cis- and trans-isomers thereof, the salts and the esters have not, however, been known to be useful as chondroprotective agents.